Ätiopathogenese des Typ-1-Diabetes mellitus

2005 ◽  
Vol 5 (04) ◽  
pp. 184-191 ◽  
Author(s):  
Thomas Kapellen ◽  
Angela Galler ◽  
Wieland Kiess ◽  
Klemens Raile
Keyword(s):  
Diabetes Mellitus ◽  
Interleukin 1 ◽  
Diabetes Mellitus Typ 1 ◽  
Tnf Α ◽  
Programmierter Zelltod ◽  
Ifn Γ ◽  
Typ 1 Diabetes

ZusammenfassungDer Diabetes mellitus Typ 1 ist eine durch Umweltfaktoren ausgelöste Autoimmunerkrankung, die genetisch empfängliche Personen trifft. Begünstigende Umweltfaktoren sind Nahrungsmittel, wie Kuhmilchprotein, virale Infekte und unterschiedliche Umweltgifte, wie Nitrosamine. Typ-1-Diabetes wird als zellvermittelte Autoimmunerkrankung mit progressiver Zerstörung der insulinproduzierenden Beta-Zellen verstanden. Dabei spielt die Aktivierung proapoptotischer Signalwege (programmierter Zelltod) durch inflammatorische Zytokine eine Schlüsselrolle beim Zelltod der β-Zellen. Den T-Lymphozyten vom so genannten Helfer-Typ (Th1) wird dabei eine zentrale Rolle zugeschrieben. Zytokine, die überwiegend von Th1-Zellen sezerniert werden, sind Interleukin-1 (IL-1)β, Interferon (IFN)-γ und Tumor-Nekrose-Faktor (TNF)α. Die Produktion dieser proinflammatorischen Zytokine wird einer Störung im fein abgestimmten Gleichgewicht zwischen Th1- und Th2-Helfer-T-Zellen zugeschrieben und führt zu einer selektiven Aktivierung von Beta-Zell-spezifischen, zytotoxischen Effektor-T-Zellen. Durch eine weitere Aufschlüsselung der Ätiopathogenese des Typ-1-Diabetes mellitus sollen neue Strategien in dessen Prävention und Heilung entwickelt werden.

scholarly journals Advanced glycation end product levels were correlated with inflammation and carotid atherosclerosis in type 2 diabetes patients

2020 ◽  
Vol 15 (1) ◽  
pp. 364-372 ◽  
Author(s):  
Jie Li ◽  
Haiyan Shangguan ◽  
Xiaoqian Chen ◽  
Xiao Ye ◽  
Bin Zhong ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Color Doppler ◽  
Enzyme Linked Immunosorbent Assay ◽  
Advanced Glycation ◽  
Advanced Glycation End Product ◽  
Inflammatory Status ◽  
Tnf Α ◽  
Ifn Γ

AbstractDiabetes mellitus with atherosclerosis (AS) adds to the social burden. This study aimed to investigate whether advanced glycation end product (AGE) levels were correlated with inflammation and carotid AS (CAS) in type 2 diabetes mellitus (T2DM) patients. A total of 50 elderly T2DM patients and 50 age-matched senior healthy subjects were recruited in this study. T2DM patients were classified into two groups based on the intima–media thickness (IMT) of the carotid artery from color Doppler ultrasonography. Patients with IMT > 1 mm were classified into the T2DM + CAS group (n = 28), and patients with IMT < 1 mm were assigned as the T2DM + non-atherosclerosis (NAS) group (n = 22). The plasma levels of AGEs, receptor for AGE (RAGE), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) of all subjects were measured by enzyme-linked immunosorbent assay. The T-lymphocyte subsets were analyzed by a flow detector. T2DM + CAS patients showed significantly higher concentrations of AGEs, RAGE, TNF-α, and IFN-γ in the peripheral blood. The highest levels of CD4+ T cells were observed in the T2DM + CAS group. The AGE level was positively correlated with the concentrations of RAGE, TNF-α, IFN-γ, and CD4+. In summary, the results showed that the levels of AGEs may be correlated with the inflammatory status in T2DM patients with CAS.

Osteoporose bei Typ-1- und Typ-2-Diabetes

2018 ◽  
Vol 16 (03) ◽  
pp. 112-117
Author(s):  
Stephan Scharla
Keyword(s):  
Diabetes Mellitus ◽  
Diabetes Mellitus Typ 2 ◽  
Diabetes Mellitus Typ 1 ◽  
Typ 2 Diabetes ◽  
Typ 1 Diabetes ◽  
Hormonelle Veränderungen

ZUSAMMENFASSUNGDiabetes mellitus und Osteoporose sind häufige Erkrankungen. Deshalb gibt es viele Patienten, die an beiden Krankheiten gleichzeitig leiden. Darüber hinaus sind jedoch sowohl der Typ-1- als auch der Typ-2-Diabetes jeweils prädisponierende Erkrankungen, die das Risiko für Osteoporose und Frakturen erhöhen. Dabei ist das Risiko bei einem Diabetes mellitus Typ 1 stärker ausgeprägt, während bei Diabetes mellitus Typ 2 vor allem Patienten mit längerer Krankheitsdauer, schlechter Stoffwechsellage, Insulinpflichtigkeit und vaskulären Folgeschäden frakturgefährdet sind. Die Knochendichte ist bei Menschen mit Typ-1-Diabetes erniedrigt, während insbesondere adipöse Typ-2-Diabetespatienten auch höhere Knochendichtewerte aufweisen können. Das Frakturrisiko wird jedoch nicht nur durch Veränderungen der Knochendichte und der Knochenarchitektur erhöht, sondern auch durch veränderte Knochenmaterialeigenschaften (veränderte Kollagen-Quervernetzung). Pathogenetische Faktoren sind Hyperglykämie, hormonelle Veränderungen und der Einfluss von oralen Antidiabetika. Während Inkretine und DPP-4-Hemmer das Frakturrisiko zu senken scheinen, sind Glitazone mit höherem Risiko assoziiert. Auch SGLT-2-Hemmer könnten bei eingeschränkter Nierenfunktion mit einem höheren Frakturrisiko behaftet sein. Die Therapie der Osteoporose bei Menschen mit Diabetes mellitus unterscheidet sich nicht vom Vorgehen bei primärer Osteoporose. Die Effizienz von antiresorptiven Medikamenten wird durch den Diabetes mellitus nicht beeinflusst.

scholarly journals Prevalência de perda auditiva, e fatores associados, em pacientes com doença renal crônica em tratamento conservador

HU Revista ◽  
2020 ◽  
Vol 46 ◽  
pp. 1-9
Author(s):  
Monik Assis Espindula Mota ◽  
Jose Otávio do Amaral Corrêa ◽  
Renato Erothildes Ferreira ◽  
Matheus Rodrigues Mendes Moraes ◽  
Bruno Parisi Marlière ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Hearing Impairment ◽  
Population Based ◽  
Hearing Disorders ◽  
Ear Diseases ◽  
Tnf Α ◽  
Ifn Γ ◽  
Survey Protocol ◽  
Population Based Survey

Introdução: A perda auditiva (PA) é uma condição cada vez mais observada na população. É encontrada com maior frequência em alguns grupos específicos como em idosos, portadores de hipertensão arterial sistêmica e diabetes mellitus. Evidências sugerem aumento da prevalência de PA em pacientes com doença renal crônica (DRC), entretanto estudos na população brasileira com DRC pré-dialítica são escassos. Objetivo: Avaliar a prevalência de perda auditiva em uma população de pacientes com doença renal crônica não dialítica e fatores associados. Material e métodos: Foi utilizada uma amostra por conveniência de pacientes com DRC não dialítica (n=159), com idade de 18 a 65 anos, em tratamento ambulatorial multidisciplinar. A acuidade auditiva foi avaliada pela audiometria tonal limiar e pelo questionário da WHO (Ear and Hearing Disorders Survey Protocol for a Population-Based Survey of Prevalence and Causes of Deafness and Hearing Impairment and other Ear Diseases) traduzido e validado para o português. Foram coletados dados sociodemográficos e clínicos, realizada ainda otoscopia, e dosagem de marcadores bioquímicos e citocinas inflamatórias TNF-α, IFN-γ, IL-1β, IL-6, IL-10, IL-17. Resultados: Nas análises, verificou-se a prevalência de 25,16% de perda auditiva neurossensorial entre os participantes. No estudo, não foi encontrada nenhuma associação entre a progressão dos estágios da DRC e o aumento de prevalência da PA, tampouco com a sua gravidade. Os marcadores sanguíneos avaliados, isoladamente ou associados à progressão do estágio da DRC, não se relacionaram à perda auditiva neurossensorial. Conclusões: Verifica-se que a prevalência de déficit auditivo na população estudada foi de 25,16%. Aconselha-se que estratégias sejam implementadas para prevenção e reversão dessa situação nesta população.  

Clinical significance of cytokine markers in children with different courses of community-acquired pneumonia

2020 ◽  
Vol 15 (5) ◽  
pp. 18-23
Author(s):  
G.P. Evseeva ◽  
◽  
G.N. Kholodok ◽  
S.V. Pichugina ◽  
S.V. Suprun ◽  
...  
Keyword(s):  
Cytokine Production ◽  
Interleukin 1 ◽  
Interferon Γ ◽  
Peripheral Blood Lymphocytes ◽  
Community Acquired Pneumonia ◽  
Enzyme Linked Immunosorbent Assay ◽  
Interleukin 17 ◽  
Monocyte Chemoattractant Protein 1 ◽  
Tnf Α ◽  
Ifn Γ

Principles of the diagnosis and treatment of community-acquired pneumonia (CAP) in children were developed and clearly formulated long ago. Nevertheless, clinicians often encounter the problem of pulmonary and pleural complications of CAP, which is challenging in terms of the choice of initial therapy, since the first symptoms of uncomplicated and complicated pneumonia are often similar. Therefore, the search for early markers of complicated CAP in children is highly important. Objective. To assess prognostic values of spontaneous and mitogen-induced cytokine production in children with CAP. Patients and methods. We have performed comprehensive examination of 108 children with CAP. Eighty-four of them had uncomplicated CAP, whereas 24 children had CAP complicated by pleurisy. We measured spontaneous and induced production of the following cytokines upon patient admission to hospital: interleukin-1 (IL-1), interleukin-17 (IL-17), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and monocyte chemoattractant protein-1 (MCP-1). To measure induced cytokine production, we stimulated peripheral blood lymphocytes by S. рneumonае (serotype 7, 11; strains 7C and 11AD). The level of cytokines was evaluated using the enzyme-linked immunosorbent assay (Vektor-BEST, Novosibirsk, Russia). Results. We found that in children with uncomplicated CAP, induction of immunocompetent blood cells (IBCs) led to increased secretion of first-generation cytokines, including IL-1, TNF-α, and IFN-γ, whereas IBCs of patients with complicated CAP primarily produced second-generation cytokines, including VEGF, МРС-1, and IL-17. Conclusion. The observed differences in spontaneous and mitogen-induced cytokine production between children with and without CAP complications suggest that these parameters can be considered as promising prognostic markers for complicated CAP in children. The proposed method can be used in pediatric practice to predict the development of complications in children with CAP. Key words: children, community-acquired pneumonia, cytokines

The Augmented Productions of Neopterin and Cytokines from Macrophages/monocytes in vitro

Pteridines ◽  
1996 ◽  
Vol 7 (3) ◽  
pp. 72-76
Author(s):  
Tadashi Lizuka ◽  
Mitsuyo Sasaki ◽  
Hitomi Kamisako ◽  
Ko Oishi ◽  
Shigeru Uemura ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Interleukin 1 ◽  
Poly I:C ◽  
Recombinant Interferon ◽  
Preliminary Examination ◽  
Tnf Α ◽  
Ifn Γ ◽  
Factor Α ◽  
Necrosis Factor

Summary In Kawasaki disease patients, increases in excretion of urinary neopterin coincided with fever and monocytosis in peripheral blood. We examined the products of neopterin, tumor necrosis factor-α (TNFα) and Interleukin-1 β (1L-1β) from healthy adult macrophages/monocytes (Mφ>/M), after stimulation with several activators to obtain some understanding of Kawasaki disease. Upon stimulation with either lipopolysaccharide (LPS) or polyinosinate-polycytidylate (Poly I:C), the Mφ/M released neopterin and pyogenic products (TNF-α or 1L-1β). The release of neopterin was eliminated by the addition of the anti-interferon-y antibody. The production of both TNF-α, 1L-1β and neopterin from Mφ/M upon stimulation of LPS was augmented in a co-culture with low dose recombinant interferon-y (rIFN-γ). Upon stimulation with rIFN-γ alone, however, the Mφ/M released neopterin but not the pyogenic products. A preliminary examination failed to detect. any difference in the response of the Mφ/M in adults annd children after stimulation with LPS. We concluded that some endotoxins could trigger the onset of Kawasaki disease and that endogenous IFN-γ can play an important role in the abnormality of Kawasaki disease patients

Operationen und akute Erkrankungen bei Typ-1-Diabetes

2020 ◽  
Vol 20 (01) ◽  
pp. 23-30
Author(s):  
Alena Gerlinde Thiele ◽  
Maren Heckenmüller ◽  
Heike Bartelt ◽  
Sabine Klamt ◽  
Thomas Michael Kapellen
Keyword(s):  
Diabetes Mellitus ◽  
Diabetes Mellitus Typ 1 ◽  
Typ 1 Diabetes ◽  
Chirurgische Eingriffe

ZUSAMMENFASSUNGEine kontinuierliche intravenöse Insulininfusionstherapie minimiert Blutzucker (BZ)-Schwankungen und damit das Risiko für Stoffwechselentgleisungen bei Kindern und Jugendlichen mit Diabetes mellitus Typ 1 (T1D), während einer Operation oder einer akuten Zweiterkrankung. Die Datenlage hinsichtlich sicherer BZ-Zielbereiche, adäquater Flüssigkeit- und Insulindosierungen während einer Insulininfusion bei pädiatrischen Patienten ist jedoch spärlich. Das hauseigene Schema zur Insulinfusionstherapie wurde nun hinsichtlich seiner Effektivität und Sicherheit in 124 Fällen bei 62 Patienten (n = 78 chirurgische Eingriffe, n = 46 akute Zweiterkrankung, mittleres Alter 9,6 ± 5,4 Jahre) evaluiert. In > 60 % der Infusionszeit lagen die BZ-Werte im Zielbereich, in nur 6 % der Zeit kam es zu kritischen Hypo- und Hyperglykämien. Damit erwies sich das Protokoll als effektiv und sicher. Allerdings erlebten Kinder < 12 Jahre signifikant mehr kritische Hypoglykämien im Vergleich zu Jugendlichen (Hypoglykämie/Fall 2,4 ± 2,7 vs. 0,9 ± 2,0; p < 0,001). Daher erscheint das Schema für Jugendliche geeigneter zu sein. Wir haben folglich das Protokoll für jüngeren Patienten durch Reduktion der Insulindosierung angepasst.

scholarly journals Analysis of Serum Cytokines in Patients with Severe Acute Respiratory Syndrome

2004 ◽  
Vol 72 (8) ◽  
pp. 4410-4415 ◽  
Author(s):  
Yuanchun Zhang ◽  
Jing Li ◽  
Yuliang Zhan ◽  
Lianqiu Wu ◽  
Xueying Yu ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Interleukin 1 ◽  
Negative Relationship ◽  
Necrosis Factor Alpha ◽  
Control Subjects ◽  
Tumor Growth Factor ◽  
Tnf Α ◽  
Ifn Γ ◽  
Novel Coronavirus ◽  
And Control

ABSTRACT Severe acute respiratory syndrome (SARS) is an acute infectious disease of the respiratory system. Although a novel coronavirus has been identified as the causative agent of SARS, the pathogenic mechanisms of SARS are not understood. In this study, sera were collected from healthy donors, patients with SARS, patients with severe SARS, and patients with SARS in convalescence. The serum concentrations of interleukin-1 (IL-1), IL-4, IL-6, IL-8, IL-10, tumor growth factor beta (TGF-β), tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ) were measured by enzyme-linked immunosorbent assays (ELISA). The concentrations of IL-1 and TNF-α were not significantly different in different groups. The IL-6 concentration was increased in SARS patients and was significantly elevated in severe SARS patients, but the IL-6 concentrations were similar in convalescent patients and control subjects, suggesting that there was a positive relationship between the serum IL-6 concentration and SARS severity. The concentrations of IL-8 and TGF-β were decreased in SARS patients and significantly reduced in severe SARS patients, but they were comparable in convalescent SARS patients and control subjects, suggesting that there was a negative relationship between the IL-8 and TGF-β concentrations and SARS severity. The concentrations of IFN-γ, IL-4, and IL-10 showed significant changes only in convalescent SARS patients. The IFN-γ and IL-4 levels were decreased, while the levels of IL-10 were increased, and the differences between convalescent SARS patients and other patient groups were statistically significant. These results suggest that there are different immunoregulatory events during and after SARS and may contribute to our understanding of the pathogenesis of this syndrome.

scholarly journals REDUCTION OF TUMOR NECROSIS FACTOR-ALPHA AND INTERFERON-GAMMA CONCENTRATION ON TUBERCULOSIS WITH DIABETES MELLITUS AS A MARKER IN DECREASE IMMUNE SYSTEM

2019 ◽  
pp. 151-154
Author(s):  
NELLY MARISSA ◽  
NUR RAMADHAN ◽  
SARI HANUM ◽  
MARLINDA ◽  
EKA FITRIA ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Immune Response ◽  
Tumor Necrosis Factor ◽  
Interferon Gamma ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Necrosis Factor

Objective: This study aimed to determine the decreased immune response of tuberculosis (TB) with diabetes mellitus (DM) patients. Methods: A total of 105 TB patients who were undergoing treatment at health centers and hospitals in Banda Aceh and Aceh Besar were included in this study. Data collection was carried out by interviewed to obtained demographic and respondent categories based on the diagnosis. Measurements of height and weight were also conducted to obtain body mass index data. 5 mL peripheral blood was taken from each respondent group into a TB with DM (TB+DM) and TB without DM (TB-DM). The blood tested usage tumor necrosis factor-alpha (TNF-α) level using enzyme-linked immunosorbent assay and interferon-gamma (IFN-γ) using IFN-γ release assay. Results: The average concentration of both TNF-α and IFN-γ was higher in TB-DM group (TNF-a 5.2 pg/mL; IFN-g 1.5 IU/mL) than in TB+DM group (TNF-a 2.06 pg/mL; IFN-g 2.86 IU/mL). There were significant differences in TNF-α between the two groups but no significant differences in IFN-γ protein concentration. Conclusion: The immune response of TB patients with DM symptoms was markedly reduced by the decreased expression of TNF-α and IFN-γ.

scholarly journals Age-Dependent Levels of Select Immunological Mediators in Sera of Healthy Children

1998 ◽  
Vol 5 (1) ◽  
pp. 28-32 ◽  
Author(s):  
Ulrich Sack ◽  
Ullrich Burkhardt ◽  
Michael Borte ◽  
Hiltrud Schädlich ◽  
Kerstin Berg ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
Physical Growth ◽  
Intercellular Adhesion Molecule ◽  
Healthy Children ◽  
Intercellular Adhesion Molecule 1 ◽  
Necrosis Factor Alpha ◽  
Age Related ◽  
Tnf Α ◽  
Age Dependent ◽  
Ifn Γ

ABSTRACT Serum cytokine levels were measured in 275 healthy children of different ages (3 to 17 years). Interleukin-1 receptor antagonist (IL-1RA), soluble IL-2R (sIL-2R) (sCD25), IL-6, IL-8, tumor necrosis factor alpha (TNF-α), soluble TNF receptor type II (sTNF-RII) (sCD120b), gamma interferon (IFN-γ), soluble intercellular adhesion molecule 1 (sICAM-1) (sCD54), soluble E selectin (sE-selectin) (ELAM-1; sCD62E), sCD14, and neopterin were measured with commercial test kits. The mean levels of IL-1RA, sIL-2R, TNF-α, sICAM-1, sE-selectin, and sCD14 were higher than in healthy adults. In contrast, IFN-γ and IL-8 were hardly detectable in children and thereby significantly lower than in adults. In the case of TNF-α, sICAM-1, sE selectin, and sCD14, there was a high interindividual variability, apparently unrelated to disease. The profiles of some cytokines, i.e., IL-1RA, IL-6, and TNF-α, showed age-related increases that overlapped with known patterns of physical growth. Of note, sIL-2R and sE-selectin instead declined with time. Because of the remarkable age-dependent variability in healthy pediatric subjects, disease-related changes, as well as therapy-dependent alterations, should be considered with caution.

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